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Molecular and Cellular Biology, March 2005, p. 1980-1988, Vol. 25, No. 5
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.5.1980-1988.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Cytoplasmic Thioredoxin Reductase Is Essential for Embryogenesis but Dispensable for Cardiac Development

Cemile Jakupoglu,1,{dagger} Gerhard K. H. Przemeck,2 Manuela Schneider,1 Stéphanie G. Moreno,3 Nadja Mayr,3 Antonis K. Hatzopoulos,3 Martin Hrabé de Angelis,2 Wolfgang Wurst,4,5 Georg W. Bornkamm,3 Markus Brielmeier,1 and Marcus Conrad3*

Department of Comparative Medicine,1 Institute of Experimental Genetics,2 Institute of Developmental Genetics, GSF Research Centre for Environment and Health, Neuherberg,4 Max Planck Institute of Psychiatry,5 Institute of Clinical Molecular Biology and Tumor Genetics, GSF, Munich, Germany3

Received 30 July 2004/ Returned for modification 1 October 2004/ Accepted 24 December 2004

Two distinct thioredoxin/thioredoxin reductase systems are present in the cytosol and the mitochondria of mammalian cells. Thioredoxins (Txn), the main substrates of thioredoxin reductases (Txnrd), are involved in numerous physiological processes, including cell-cell communication, redox metabolism, proliferation, and apoptosis. To investigate the individual contribution of mitochondrial (Txnrd2) and cytoplasmic (Txnrd1) thioredoxin reductases in vivo, we generated a mouse strain with a conditionally targeted deletion of Txnrd1. We show here that the ubiquitous Cre-mediated inactivation of Txnrd1 leads to early embryonic lethality. Homozygous mutant embryos display severe growth retardation and fail to turn. In accordance with the observed growth impairment in vivo, Txnrd1-deficient embryonic fibroblasts do not proliferate in vitro. In contrast, ex vivo-cultured embryonic Txnrd1-deficient cardiomyocytes are not affected, and mice with a heart-specific inactivation of Txnrd1 develop normally and appear healthy. Our results indicate that Txnrd1 plays an essential role during embryogenesis in most developing tissues except the heart.

* Corresponding author. Mailing address: Institute of Clinical Molecular Biology and Tumor Genetics, GSF, Marchioninistr. 25, D-81377 Munich, Germany. Phone: 49-89-7099525. Fax: 49-89-7099500. E-mail: Marcus.Conrad{at}gsf.de.

{dagger} Present address: Institut für Rekonstruktive Neurobiologie, Rheinische Friedrich-Wilhelms-Universität, D-53105 Bonn, Germany.

Molecular and Cellular Biology, March 2005, p. 1980-1988, Vol. 25, No. 5
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.5.1980-1988.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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